Metabolomic Study of High-Fat Diet-Induced Obese (DIO) and DIO Plus CCl<sub>4</sub>-Induced NASH Mice and the Effect of Obeticholic Acid

Nanlin Zhu; Suling Huang; Qingli Zhang; Zhuohui Zhao; Hui Qu; Mengmeng Ning; Ying Leng; Jia Liu

doi:10.3390/metabo11060374

Metabolites (Jun 2021)

Metabolomic Study of High-Fat Diet-Induced Obese (DIO) and DIO Plus CCl<sub>4</sub>-Induced NASH Mice and the Effect of Obeticholic Acid

Nanlin Zhu,
Suling Huang,
Qingli Zhang,
Zhuohui Zhao,
Hui Qu,
Mengmeng Ning,
Ying Leng,
Jia Liu

Affiliations

Nanlin Zhu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Suling Huang: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Qingli Zhang: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Zhuohui Zhao: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Hui Qu: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Mengmeng Ning: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Ying Leng: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Jia Liu: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

DOI: https://doi.org/10.3390/metabo11060374
Journal volume & issue: Vol. 11, no. 6
p. 374

Abstract

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The pathophysiology of nonalcoholic fatty liver disease (NAFLD) is a complex process involving metabolic and inflammatory changes in livers and other organs, but the pathogenesis is still not well clarified. Two mouse models were established to study metabolic alteration of nonalcoholic fatty liver and nonalcoholic steatohepatitis, respectively. The concentrations of metabolites in serum, liver and intestine content were measured by the AbsoluteIDQ® p180 Kit (Biocrates Life Sciences, Innsbruck, Austria). Multivariate statistical methods, pathway analysis, enrichment analysis and correlation analysis were performed to analyze metabolomic data. The metabolic characteristics of liver, serum and intestine content could be distinctly distinguished from each group, indicating the occurrence of metabolic disturbance. Among them, metabolic alteration of liver and intestine content was more significant. Based on the metabolic data of liver, 19 differential metabolites were discovered between DIO and control, 12 between DIO-CCl4 and DIO, and 47 between DIO-CCl4 and normal. These metabolites were mainly associated with aminoacyl-tRNA biosynthesis, nitrogen metabolism, lipid metabolism, glyoxylate and dicarboxylate metabolism, and amino metabolism. Further study revealed that the intervention of obeticholic acid (OCA) could partly reverse the damage of CCl4. The correlation analysis of metabolite levels and clinical parameters showed that phosphatidylcholines were negatively associated with serum alanine aminotransferase, aspartate aminotransferase, NAFLD activity score, and fibrosis score, while lysophosphatidylcholines, sphingomyelins, amino acids, and acylcarnitines shared the reverse pattern. Our study investigated metabolic alteration among control, NAFLD model, and OCA treatment groups, providing preclinical information to understand the mechanism of NAFLD and amelioration of OCA.

Published in Metabolites

ISSN: 2218-1989 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/metabolites

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